Many experiments have demonstrated that early experience dramatically influences brain and behavior development. However, little is known regarding the cellular events underlying these processes. The long-term objective of our research is to understand the cellular mechanism by which interactions between neurons and their environment regulates central nervous system development and maintenance. We have been examining this question in the chick brain stem auditory nuclei, where the specificity and relative simplicity of connections make them uniquely well-suited to such investigations. Previous experiments have shown that removal of afferent input experts a rapid, age-dependent, and often deleterious effect on target neurons. This grant proposes to answer three specific questions. First, what is the presynaptic "signal" that regulates the postsynaptic response? We will examine this question by specifically manipulating several aspects of afferent input, including pre- and postsynaptic electrophysiological activity, and axoplasmic transport to sort out their relative contributions to the regulatory process. Second, what is the cellular chain of events which underlies the postsynaptic response? We will examine both ultrastructural and biochemical features of target neurons undergoing cell death. Finally, why are neurons in adult birds seemingly immune to the effects of deafferentation? We will investigate the normal metabolism, innervation, and physiological characteristics of auditory neurons in adult birds to determine whether there is a relationship between any of these variables and neuronal responses to manipulations of afferent activity and integrity. The information gained from these studies will be of importance in understanding the basic processes of cellular regulation as well as in understanding and hopefully preventing the deleterious effects of central nervous system injury.